Linnaeus Therapeutics has dosed the first patient in its phase 1/2 adaptive-design clinical trial of its lead-product-candidate, LNS8801, in combination with KEYTRUDA? (pembrolizumab) in patients who had previous clinical benefit from immune checkpoint inhibitors and then subsequently progressed. This marks the first time any company has dosed a patient in a clinical trial specifically targeting the G protein-coupled estrogen receptor (GPER) in combination with pembrolizumab. The initiation of the study follows the successful identification of the recommended phase 2 dose (RP2D) in the Company's ongoing study of LNS8801.

LNS8801 is an orally bioavailable small molecule that is a highly specific and potent agonist of the GPER. LNS8801 is currently finishing the dose escalation portion of its phase 1/2 study assessing the safety, tolerability, pharmacokinetics and preliminary efficacy in patients with advanced cancer.

"We are extremely pleased to begin testing LNS8801 in combination with pembrolizumab in this patient population. In our phase 1 trial of LNS8801 we have seen biological and clinical signals that suggest LNS8801 in combination with pembrolizumab may have activity based on the preclinical rationale and reverse resistance to immune checkpoint inhibitors. We currently have six outstanding academic comprehensive cancer centers all enthusiastically recruiting patients for this promising study," said Patrick Mooney, MD, chief executive officer of Linnaeus. "We believe that LNS8801 with pembrolizumab has potential to provide meaningful clinical benefit for patients with cancer, and we look forward to providing updates over the course of the study."

The study entitled, "A Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of LNS8801 in Patients with Advanced Cancer Including Immunotherapy Refractory Expansion Cohorts with and without Pembrolizumab," was designed in two parts. The phase 1 dose-escalation portion of the trial assessed the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of LNS8801. Data from the study has allowed Linnaeus to determine the RP2D and safely open the phase 2 dose-expansion cohorts. Linnaeus anticipates opening several more phase 2 dose-expansion cohorts exploring LNS8801 activity as a monotherapy and in combination with other compounds in defined patient populations in the coming year.

LNS8801 is an orally bioavailable and highly specific agonist of GPER whose activity is dependent on the expression of GPER. GPER activation suppresses well-known tumor-associated genes, such as c-Myc and PD-L1. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing phase 1/2 study in humans, LNS8801 monotherapy has been safe and well-tolerated. Additionally, LNS8801 has demonstrated target engagement and clinical benefit in advanced cancer patients. Data from the phase 1/2 study is anticipated to be presented in a peer-reviewed setting in 2021.